AB1426 PREDICTORS OF RHEUMATIC TOXICITIES OF IMMUNE CHECKPOINT INHIBITORS AND CANCER OUTCOMES IN PATIENTS WITH ADVANCED MELANOMA
Authors: A. Bruce, A. Menzies, G. Long, B. Fernandes, F. Joshua
Journal: Annals of the Rheumatic Diseases (2022)

Background Immune checkpoint inhibitors (ICIs) including monoclonal antibodies to PD-1 and CTLA-4 have activity across various cancers. Dedicated cohort studies have examined the epidemiology and clinical course of rheumatic toxicities (1–3) and the effect of pre-existing autoimmune disease has been explored (4), with limited assessment of the effect of non-immune mediated rheumatic disease (3). A positive association between ICI-induced rheumatic disease and favourable cancer outcomes has been suggested (1,2), although derived from heterogenous cancer populations. Objectives To identify risk factors for the development of ICI-induced rheumatic disease and predictors of cancer outcomes in patients with advanced melanoma. Methods A single-centre observational study of patients with stage III or IV melanoma receiving all available ICI therapies, who completed a for-purpose questionnaire to capture rheumatic symptoms and risk factors upon recruitment and at 12-months. Symptom severity was assessed according to patient reported measures such as visual analogue scale (VAS) scores for pain. Clinical details were extracted from patients’ medical records. Predictors of rheumatic toxicities and cancer outcomes were identified through regression analysis. Results Amongst 147 eligible patients, the prevalence of new or worsening rheumatic symptoms was 32.5% at recruitment and 21% at 12 months. The incidence of documented arthralgia, inflammatory arthritis and PMR-like syndrome was 39.5%, 5.4% and 3.4% respectively. Binary logistic regression identified pre-existing symptomatic rheumatic disease, including non-immune mediated rheumatic disease, as the primary risk factor for developing rheumatic toxicities (OR 3.161). Continuation of ICI therapy (OR 16.52), followed by rheumatic toxicities (OR = 4.368) were predictors of favourable tumour response. Conclusion Rheumatic toxicities of ICI therapy commonly affect patients with melanoma and are more likely to occur in patients with pre-existing autoimmune and non-immune mediated rheumatic disease. Continuation of ICI therapy improves cancer outcomes and can be facilitated by early detection of rheumatic symptoms using patient reported outcome measures. Table 1. Bivariate logistic regression of predictors of patient-reported rheumatic toxicity. Sig., Significance; OR, Odds ratio; CI, confidence interval; BRAF/MEK, BRAF and MEK inhibitors; PD-1, Programmed Cell Death protein – 1; CTLA-4, Cytotoxic T-lymphocyte-associated protein. Figure 1. A) Receiver-operator curve for accuracy of binary logistic regression model clinician-recorded rheumatic disease. (B) Area under receiver-operator curve. Test result variable(s): predicted probability. AUROC, Area Under Receiver-Operator Curve; Std. Error, Standard Error; Sig., Significance. (a) Under the nonparametric assumption (b) Null hypothesis: true area = 0.5 References [1]Kostine M, Rouxel L, Barnetche T, Veillon R, Martin F, Dutriaux C, et al. Rheumatic disorders associated with immune checkpoint inhibitors in patients with cancer-clinical aspects and relationship with tumour response: a single-centre prospective cohort study. Ann Rheum Dis. 2018;77(3):393–8. [2]Braaten TJ, Brahmer JR, Forde PM, Le D, Lipson EJ, Naidoo J, et al. Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation. Ann Rheum Dis. 2019;332–8. [3]Buder-Bakhaya K, Benesova K, Schulz C, Anwar H, Dimitrakopoulou-Strauss A, Weber TF, et al. Characterization of arthralgia induced by PD-1 antibody treatment in patients with metastasized cutaneous malignancies. Cancer Immunol Immunother. 2018;67(2):175–82. [4]Menzies AM, Johnson DB, Ramanujam S, Atkinson VG, Wong ANM, Park JJ, et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann Oncol. 2017;28(2):368–76. Disclosure of Interests Alana Bruce: None declared, Alexander Menzies Consultant of: A.M.M. has participated in advisory boards for BMS, MSD, Novartis, Roche, Pierre-Fabre, Georgina Long Consultant of: GVL is consultant advisor for Aduro Biotech Inc, Agenus Inc, Amgen Inc, Array Biopharma inc, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Evaxion Biotech A/S, Hexel AG, Highlight Therapeutics S.L., Merck Sharpe &amp; Dohme, Novartis Pharma AG, OncoSec, Pierre Fabre, QBiotics Group Limited, Regeneron Pharmaceuticals Inc, Specialised Therapeutics Australia Pty Ltd., Brian Fernandes: None declared, Fredrick Joshua Consultant of: F.J. has performed clinical trials and participated in advisory boards for Abbvie, Pfizer, Novartis, Sanofi, Eli Lily and Roche